Biology yeMolecular yeRNA Virus
Mavhairasi eRNA iboka remavhairasi ane majini anosanganisira ribonucleic acid (RNA). Boka iri rinosanganisira hutachiona hwakawanda hunokosha muvanhu, mhuka, nemiti, zvakaita sefuruwenza, dengue, hepatitis C, polio, rabies, measles, uye SARS-CoV-2. Kusiyana kwemavhairasi eRNA kuri munzira dzawo dzekubereka, mwero wekuchinja kukuru, uye nzira dzekudzivirira immune system. Kunzwisisa molecular biology yemavhairasi eRNA kwakakosha pakugadzira majekiseni, mishonga inorwisa mavhairasi, uye masisitimu ekuongorora chirwere.
1. Maumbirwo ejini uye kurongeka kwemavhairasi eRNA
Kazhinji, majini eRNA virus anogona kuva single-stranded (ssRNA) kana double-stranded (dsRNA). Mu ssRNA, genome inogona kuva positive-sense (+RNA) kana negative-sense (−RNA). +RNA viruses dzine majini anogona kushanda zvakananga se mRNA, saka anoshandurwa nekukurumidza ne ribosomes dze host cell mushure mekupinda mu cytoplasm. Mienzaniso inosanganisira Picornaviridae (semuenzaniso, poliovirus) uye Flaviviridae (semuenzaniso, dengue). Kusiyana neizvi, −RNA viruses (semuenzaniso, furuwenza nerabies) dzine majini anoenderana ne mRNA, saka anofanira kutanga anyorerwa kuita mRNA nema enzymes eviral asati ashandurwa.
Majini evhairasi yeRNA anogonawo kupatsanurwa kana kusapatsanurwa. Furuwenza ine genome yakapatsanurwa, iyo inobvumira "kupatsanurwazve," kuchinjana kwezvikamu pakati pevhairasi kana ichibata sero rimwe chete. Chiitiko ichi chinogona kugadzira mhando itsva dzinogona kukonzera kubuda kukuru. Panguva iyi, mavhairasi mazhinji eRNA ane genome imwe chete, refu inowanzo gadzira polyprotein, iyo inozopatsanurwa kuita mapuroteni anoshanda.
Pamusoro pemapuroteni-coding sequences (open reading frames/ORFs), maRNA viral genomes ane zvinhu zvisina coding pamagumo e5' ne3' izvo zvakakosha pakudzokororwa kweRNA, kushandurwa, uye kugadzikana. Maumbirwo echipiri akadai sehairpins nepseudoknots anowanzo ratidza kubatana kwemapuroteni evirusi uye zvinhu zvinobata masero emuviri.
2. Kupinda kwehutachiona uye kuburitswa kwegenome (kusunungura)
Kutenderera kwehupenyu hwevhairasi yeRNA kunotanga kana yakabatana nereceptor yemasero emuviri. Kudyidzana uku kunosarudza tropism yematishu uye specificity yemuviri. Mushure mekunamira, vhairasi inopinda kuburikidza ne endocytosis kana membrane fusion. Mavhairasi akavharirwa, akadai sefuruwenza ne coronaviruses, anowanzo shandisa membrane fusion, nepo mavhairasi mazhinji asina kuvharirwa achipinda kuburikidza ne endocytosis uye ozochinja chimiro kuti abudise capsid yawo.
Maitiro ekusunungura RNA genome kubva mu capsid - idanho rakakosha. Kana RNA ikasaburitswa panzvimbo chaiyo nenguva chaiyo, kudzokororwa hakuzoitiki. Mune mamwe mavhairasi, pH yakaderera mu endosome inokonzera shanduko muchimiro chemapuroteni evhairasi, zvichiita kuti genome ibude ichipinda mu cytoplasm.
3. Shanduro: mashandisiro anoita mavhairasi ribosomes
Nekuti mavhairasi haana ribosomes, anovimba nemichina yekushandura yemasero emugadziri. Mavhairasi eRNA anogona kushandurwa zvakananga, asi anofanira kukunda zvipingamupinyi zvakati wandei: kukwikwidzana nemRNA yesero, kudiwa kwe "cap" pamagumo e5', uye nzira dzekudzora mhando dzesero.
Mamwe mavhairasi ane magumo mashanu akavharirwa semugadziri we mRNA (semuenzaniso, ma coronaviruses), nepo mamwe achishandisa dzimwe nzira, dzakadai se internal ribosome entry site (IRES) mu picornaviruses, izvo zvinobvumira ribosome kutanga kushandura isina chivharo. Mavhairasi, akadai sefuruwenza, anoshandisawo "cap-snatching," achiba chivharo kubva kumugadziri we mRNA kuti chishandiswe pa viral mRNA yavo. Nzira idzi dzakakosha mu molecular biology yemavhairasi eRNA, sezvo ari iwo anogona kutapukirwa nemishonga inorwisa mavhairasi.
Mumavhairasi mazhinji eRNA, genome inoshandurwa kuita polyprotein imwe chete hombe. Polyprotein iyi inozogadziriswa nemavhairasi proteases (kana kuti host proteases) kuita mapuroteni echimiro uye asiri echimiro. Saka mavhairasi protease ndiwo anonyanya kushandiswa pakurapa, sezvinoonekwa mukurapa hepatitis C neCOVID-19.
4. Kudzokororwa kweRNA: basa reRNA polymerase inotsamira paRNA
Chinhu chinonyanya kusiyanisa mavhairasi eRNA kushandisa kwawo enzyme inonzi RNA-dependent RNA polymerase (RdRp), polymerase inokwanisa kukopa RNA kubva muRNA template. Masero evanhu haana RdRp ye cytoplasmic RNA replication, saka iyi enzyme inowanzo nyorwa nevhairasi uye inyanzvi chaiyo yekurwisa mushonga.
Maitiro ekukopa anowanzo itika mu "mafekitori ekukopa," kana membrane compartments dzakagadziriswazve nemavhairasi anobva kumasero emuviri (semuenzaniso, endoplasmic reticulum). Macompartments aya anobatsira kutarisisa zvinhu zvinokopa uye kudzivirira hutachiona hweRNA kubva kuma sensors ekudzivirira muviri.
Pamavhairasi e +RNA, RdRp inotanga yagadzira tambo ye α-RNA senzira yepakati, uye kubva patemplate iyi ye α-RNA, makopi matsva akawanda e α-RNA anogadzirwa. Pamavhairasi e α-RNA, RdRp inofanira kuita basa rekunyora pakutanga kwehutachiona kuti igadzire mRNA. Kazhinji, RdRp inoshanda pamwe chete nema cofactor akadai se helicases (kusunungura chimiro cheRNA) uye nucleotidyltransferases (kuumbwa kwecap kana kugadziriswa kwemagumo eRNA).
5. Kuchinja-chinja, kufungidzira, uye kushanduka-shanduka nekukurumidza
RdRp inowanzo shaya kugona kwekuongorora DNA polymerase, zvichikonzera kuwanda kwekuchinja kwemavhairasi eRNA. Izvi zvinoguma nehuwandu hwemavhairasi hunoumba "quasispecies," muunganidzwa wemhando dzakasiyana-siyana dziri mukati memunhu mumwe chete. Iyi mukana wehupenyu ndeyekukurumidza kugadzirisa kumanikidzwa kwesarudzo, senge ma antibodies, mishonga yekudzivirira mavhairasi, kana kusiyana kwenzvimbo dzenyama.
Zvisinei, huwandu hwakawanda hwekuchinja hunogonawo kukonzera "dambudziko rekutadza," kuunganidzwa kwekuchinja kunokanganisa hutachiona uko kunoita kuti hutachiona hurasikirwe nehupenyu. Mimwe mishonga inorwisa mavhairasi inoshandisa pfungwa iyi nekuwedzera zvikanganiso zvekudzokororwa kwehutachiona. Zvinofadza kuti, ma coronavirus akasiyana, ane enzyme inoongorora (exoribonuclease) inoderedza huwandu hwekuchinja huchienzaniswa nemamwe mavhairasi eRNA, zvichivabvumira kuchengetedza majini makuru.
6. Kutaurwa kwemajini: subgenomics, frameshifting, uye regulation
Mavhairasi eRNA anoshandisa nzira dzakasiyana-siyana dzemamorekuru kuti awedzere ruzivo rwemajini mukati memajini avo madiki. Muenzaniso kuumbwa kwema mRNA ari pasi pemajini mu coronaviruses, izvo zvinogonesa kuratidzwa kwemapuroteni emukati kubva kunzvimbo dzakatarwa dze genome. Kunewo mashandiro e ribosomal frameshifting, ayo anochinja chimiro chekuverenga panguva yekushandura kuitira kuti RNA imwe chete igone kugadzira mapuroteni akasiyana-siyana. Dzimwe nzira dzinosanganisira kumisa kuverenga kwe codon uye kushandiswa kwe internal promoters mune mamwe mavhairasi.
Kudzora kutaurwa kwemajini kunowanzo batanidzwa nekutevedzana kweRNA uye chimiro, pamwe nekudyidzana nemapuroteni ehutachiona uye emuviri. Zvinhu izvi zvinopesvedzera panowanikwa mapuroteni ekudzokorora, apo mapuroteni echimiro anova nesimba, uye kuti hutachiona hunotsausa sei zviwanikwa zvemasero.
7. Kuunganidza nekuburitsa
Mushure mekunge mapuroteni matsva e genome nema structural proteins agadzirwa, hutachiona hunounganidza chinhu chitsva. Kuungana kunosanganisira kurongedza RNA mu capsid, iyo inowanzo shandiswa pakuisa masaini mukati meRNA. Mavhairasi asina kuvharwa anowanzo buda kuburikidza ne cell lysis, nepo mavhairasi akavharirwa achibuda kuburikidza ne cell membrane kana organelle, achishandisa chikamu che membrane se envelopu. Maitiro ekugadzira anoda kubatana kwema matrix proteins, envelopu glycoproteins, uye cellular factors.
8. Kudyidzana nemasoja emuviri uye nzira dzekudzivirira
RNA yehutachiona inozivikanwa nemasensa emuviri ekudzivirira muviri akadai seRIG-I neMDA5, ayo anoona RNA yekunze kana maumbirwo chaiwo. Kuonekwa uku kunotanga kugadzirwa kweinterferon uye kushanda kwemajini akawanda ekudzivirira utachiona. Kuti ararame, mavhairasi eRNA anogadzira mapuroteni e-interferon-antagonist, anovanza RNA yavo kuburikidza nekuvharira uye methylation, kana kuvanza kudzokororwa kwayo mukati mezvikamu zvemembrane.
Kurwisana uku kwemamorekuru kunosarudza huwandu hwehutachiona uye mhedzisiro yehutachiona. Kuchinja kudiki mumapuroteni ekudzivirira muviri kunogona kushandura kugona kwehutachiona kupararira kana kukonzera chirwere chakakomba.
9. Zvinorehwa nekurapwa, majekiseni, uye kuongororwa kwechirwere
Ruzivo rwemamorekuru eRNA viruses ndiyo hwaro hwekuvandudzwa kwezvekurapa. RdRp nemavirus proteases mishonga inokwezva nekuti inokosha uye yakanangana. Padivi rekudzivirira, kunzwisisa mapuroteni epamusoro uye dynamics yekuchinja kwakakosha pakugadzira maantigen akagadzikana. Kuongorora mamorekuru senge RT-PCR kunoshandisa chokwadi chekuti genome yevirusi iRNA, zvichiita kuti pave nedanho rekushandura RNA kuita DNA isati yawedzerwa.
Pamusoro pezvo, kuongorora majini kunobatsira kutevera kushanduka kwemavhairasi eRNA uye kuona mhando itsva. Izvi zvakakosha zvikuru kumavhairasi anochinja-chinja nekukurumidza kana ari panjodzi yekusanganiswazve.
Mhedziso
Biology yemamorekuru emavhairasi eRNA inoratidza kuti zvipenyu zviri nyore zvinogona kushandisa nzira dzakaoma dzekurarama nadzo: kupinda mumasero, kushandisa ribosomes dzemugadziri, kukopa majini kuburikidza neRdRp, kushanduka nekukurumidza kuburikidza nekuchinja kwemuviri, uye kudzivirira immune system. Kunzwisisa zvakadzama maitiro aya hakungokoshi chete kune sainzi yekutanga yehutachiona asiwo kunoisa hwaro hwekudzora zvirwere kuburikidza nemajekiseni, mishonga inorwisa mavhairasi, uye matekinoroji emazuva ano ekuongorora. Nekuwedzera kwenjodzi yezvirwere zvinotapukira, kudzidza mavhairasi eRNA kucharamba kuri munda unokosha uye unokurumidza kukura.
